BACKGROUND: Higher prevalence of nonalcoholic fatty liver disease (NAFLD) in men and postmenopausal women than in premenopausal women has suggested a potential role of sex hormones in the pathogenesis of the disease. We sought to evaluate the association between oral contraceptive pills (OCP) and NAFLD and to determine whether adiposity mediates any effect.METHODS: We included 4338 women aged 20-60 years who were enrolled in the Third National Health and Nutrition Examination Survey from 1988 to 1994 in a population-based cross-sectional study. We defined NAFLD as moderate-severe steatosis on ultrasonography in women without excessive alcohol use or other identifiable causes. OCP use was based on self-report and was categorized as never, former or current use.RESULTS: The overall weighted prevalence of NAFLD was 11.6 % but lower in current (6.7 %) than in former (12.0 %) or never users (15.6 %, P = 0.016). In the multivariable model, current OCP users experienced a 50 % lower odds of NAFLD than never users (adjusted odds ratio 0.50; 95 % confidence interval 0.26, 0.98) after adjusting for age, race/ethnicity, smoking status, history of diabetes or hypertension and education. Further adjustment for body mass index or waist circumference significantly attenuated the OCP-NAFLD relationship.CONCLUSIONS: In this large US-representative population, OCP use was associated with reduced odds of NAFLD. However, this association could be mediated or confounded by adiposity. Prospective studies are needed to further clarify the causal role of sex hormone.